1	Advisory Committee Discussion Points
2	1. Patient Populations a. Which patient populations are strongly recommended for inclusion at the time of initial approval? In particular, comment on: stage of disease (compensated and decompensated cirrhosis) treatment experience (naïve and interferon+ ribavirin experienced) genotype (1 and 4 or 2 and/or 3 or some other grouping) co-morbidities (HIV and/or HBV co-infection) pre and post liver transplantation pediatrics racial and ethnic groups
3	1. Patient Populations b. For the purposes of pursuing an indication for novel agents in treatment experienced non responder patients please comment on the following components as inclusion criteria in clinical development studies Previously treated with 1 or more IFN-containing regimens that include PEG-IFN and RBV; and Failure to achieve a ≥ 2 log reduction in HCV RNA at Week 12, or HCV detectability at Week 24 or beyond while on therapy (confirmed by a repeat test); and Compliance documented over the first 12 weeks of previous therapy to confirm receipt of at least 80% of the prescribed RBV and PEG-IFN dose.
4	1. Patient Populations c. Please discuss whether or not it is appropriate in a clinical trial of prior interferon treatment non- responders to study true responders, partial responders and relapsers together and why.
5	2. Selection of Controls Are placebo controls or delay of initiation of therapy acceptable, and, if so, of what duration? In your answer, please consider the following patient populations: treatment-naïve versus treatment-experienced compensated and decompensated liver disease.
6	3. Study Design-Evaluation of Efficacy Endpoints Compensated Liver Disease Considering the patient populations identified in question number 1 and the necessity that endpoints for registration be clinically meaningful, please answer the following: a. Which primary endpoint (s) should be used in clinical trials? Please discuss histologic, viral and biochemical endpoints.
7	3. Study Design-Evaluation of Efficacy b. When should the assessment of the primary endpoint be made? Please comment on the pros and cons of an SVR 12 (12 weeks after cessation of treatment) versus SVR 24 (24 weeks after cessation of treatment).
8	3. Study Design-Evaluation of Efficacy c. If a study has treatment arms of a different duration, when should assessment of SVR 24 be made? Specifically, should it be made 24 weeks after end of treatment for all arms, or 24 weeks after the end of treatment based on the arm with the longest duration of therapy?
9	3. Study Design-Evaluation of Efficacy d. Please discuss the following study designs adding the investigational agent to standard-of-care (SOC) use of a dose of PEG-IFN lower than SOC or lower than SOC and of shorter duration + investigational agent ribavirin substitution use of two or more investigational agents monotherapy
10	3. Study Design-Evaluation of Efficacy e. What degree of change is clinically meaningful for patients with decompensated liver disease when using change in CPT or MELD score as an endpoint?
11	4. Long Term Follow-Up Beyond the assessment of the primary endpoint for registration, what is the appropriate duration of follow-up for chronic hepatitis C infection, and what kind of information should be gathered? Please discuss duration of follow-up for different patient populations (especially pediatrics), and, in particular, when an investigational agent is not added to standard-of-care.